Sweden's Magnus Norman became the ninth victim in the men's singles, back spasms forcing him to retire at the start of the second set of his match against Gustavo Kuerten, the Brazilian No 5 seed, who advanced to the quarter-finals.
"I'm worried about this Creatine players are being encouraged to take," said McEnroe, who is commentating for USA Network. "Some of the guys have arms the size of some of our legs now. It's legal, but if you listen to the guys on the circuit, they say it causes cramping and muscle pulls."
He added: "I don't know who is taking it, and who is not. But it's not a good idea to be taking this stuff. It's getting out of hand. It's hard to believe so many players have fallen to injury. I blame it on the pursuit of extra power."
Pete Sampras and Mark Philippoussis withdrew before start of the tournament, Sampras damaging his lower back during practice on the eve of the event, Philippoussis spraining an ankle playing basketball.
Pat Rafter, champion for the past two years, retired because of a shoulder injury at the start of the fifth set of his first-round match against Cedric Pioline. Blisters accounted for Julien Boutter in the first round.
A back injury struck Carlos Moya after the No 8 seed lost the first two sets against Nicolas Escude in the second round. Jan-Michael Gambill retired after cramping during the fifth set of his second-round match against Fabrice Santoro, who quit through exhaustion when two sets and 5-1 down to Jiri Novak in the third round.
Todd Martin, the No 7 seed, advanced to meet Greg Rusedski in the fourth round when a knee injury caused Magnus Larsson to default after losing the opening set.
Norman, a finalist in the Long Island tournament on the eve of the Open, said he was aware that other players had taken Creatine. "I've never taken it, and I'm actually against it," he said. "I've never taken it, and I never will."
He added: "I felt very, very fresh going into this tournament. just had a lot of bad luck today."
Only two players have been forced to retire in the women's singles: Henrieta Nagyova, whose wrist injury gave Venus Williams a walk-over to the fourth round, and Amelie Cocheteux, who was struck by a virus during the opening set of her third-round match against her French compatriot, Julie Halard- Decugis.
Mary Pierce, who is due to meet Lindsay Davenport, the defending champion, in the quarter-finals, admits that she has taken Creatine. The Women's Tennis Association made a statement earlier in the year, stressing that Creatine is not banned, and that athletes in some other sports had been known to take Creatine with other substances.
McEnroe, who is expected to broaden his role in the sport by being appointed to captain the US Davis Cup team next year, in place of Tom Gullikson, has other theories about the spate of injuries in the men's game.
"It's the schedule," he said. "This hideous system that the men's tour has had the last 10 years. That's the best-of-14 system." Only a player's best 14 results during a rolling 12-month period count in the rankings.
"It encourages players to play more," McEnroe said. "What they should be doing, instead, is playing less and really focusing for each and every match they play, making each match count for something."
Norman said though the schedule was great. "I love to play tennis. If there were tournaments during the whole year, I would play every week."
All is not doom and gloom here. Jana Novotna, the 1998 Wimbledon women's singles champion, made sure that the announcement that she would retire at the end of the year was not a solemn occasion.
Asked if the Duchess of Kent knew about her decision, Novotna said: "Yes, I called her last night, actually. She said, `Don't do it'. I said: `I have to. I'm still going to come, because I have the badge'."Reuse content